Fernanda Arantes-costa - Academia.edu (original) (raw)

Papers by Fernanda Arantes-costa

Research paper thumbnail of Qualidade de vida do estudante de medicina

Revista de Medicina, 2019

Introdução: A qualidade de vida e a saúde mental dos estudantes de medicina podem afetar o seu de... more Introdução: A qualidade de vida e a saúde mental dos estudantes de medicina podem afetar o seu desempenho acadêmico, suas habilidades e atitudes com pacientes. Evidências recentes confirmam a importância do ambiente educacional como um dos determinantes da saúde mental e qualidade de vida. Este estudo teve o objetivo de avaliar diferentes aspectos da qualidade de vida dos estudantes de medicina brasileiros em todos os anos do curso. Casuística e Métodos: Estudo transversal de abrangência nacional, com a utilização de questionário validado de qualidade de vida específico para o estudante da área da saúde (Veras-q). Resultados: De uma amostra aleatória de 1.650 estudantes, em 22 escolas médicas de diferentes regiões do país, 1.350 (81,8%) participaram do estudo. Os coeficientes de alfa Cronbach dos domínios do Veras-q variaram entre 0,77 e 0,82. Estudantes do sexo feminino apresentaram menores escores de qualidade de vida nos domínios físico, psicológico e uso do tempo, quando compara...

Research paper thumbnail of The COVID-19 pandemic: time for medical teachers and students to overcome grief

Research paper thumbnail of Inhibition of Inflammation and Mucus Production By Bordetella Pertussis Whole-Cell Vaccine in a Murine Model of Allergic Rhinitis

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Sensitization by subcutaneous route is superior to intraperitoneal route in induction of asthma by house dust mite in a murine mode

Einstein (São Paulo), 2015

To develop a new experimental model of chronic allergic pulmonary disease induced by house dust m... more To develop a new experimental model of chronic allergic pulmonary disease induced by house dust mite, with marked production of specific immunoglobulin E (IgE), eosinophilic inflammatory infiltrate in the airways and remodeling, comparing two different routes of sensitization. The protocol lasted 30 days. BALB/c mice were divided into six groups and were sensitized subcutaneously or intraperitoneally with saline (negative control), Dermatophagoides pteronyssinus (Der p) 50 or 500 mcg in three injections. Subsequently they underwent intranasal challenge with Der p or saline for 7 days and were sacrificed 24 hours after the last challenge. We evaluated the titration of specific IgE anti-Der p, eosinophilic density in peribronchovascular space and airway remodeling. Both animals sensitized intraperitoneally and subcutaneously produced specific IgE anti-Der p. Peribronchovascular eosinophilia increased only in mice receiving lower doses of Der p. However, only the group sensitized with Der p 50 mcg through subcutaneously route showed significant airway remodeling. In this murine model of asthma, both pathways of sensitization led to the production of specific IgE and eosinophilia in the airways. However, only the subcutaneously route was able to induce remodeling. Furthermore, lower doses of Der p used in sensitization were better than higher ones, suggesting immune tolerance. Further studies are required to evaluate the efficacy of this model in the development of bronchial hyperresponsiveness, but it can already be replicated in experiments to create new therapeutic drugs or immunotherapeutic strategies.

Research paper thumbnail of Effects of acute hypochlorite exposure in OVA-sensitized and challenged mice

European Respiratory Journal, 2015

Research paper thumbnail of BmTI-A, a serine protease inhibitor, reduces the chronic allergic lung inflammation in a mice model

European Respiratory Journal, 2015

Research paper thumbnail of Inflammatory and functional responses after (bio)diesel exhaust exposure in an asthmatic mice model – A comparison between diesel and biodiesel

European Respiratory Journal, 2015

Research paper thumbnail of Efeitos do resíduo da queima de óleo diesel (ROFA) e da inflamação pulmonar alérgica crônica em três linhagens de camundongos

Research paper thumbnail of Bordetella Pertussis Whole-Cell Vaccine Inhibits Specific IgE, Inflammation and Airway Remodeling in a Murine Model of Asthma

Journal of Allergy and Clinical Immunology, 2015

RATIONALE: Axon reflex theory was proposed to explain the involvement of afferent airway nerves i... more RATIONALE: Axon reflex theory was proposed to explain the involvement of afferent airway nerves in regulation allergic asthma phenotypes. Thus, afferent airway nerve ablation affects asthma phenotype in the ovalbumin (OVA) allergic asthma model. The regulation of asthma phenotypes by transient receptor potential A1 (TRPA1) in the OVA model has also been reported. Since TRPA1 is mainly expressed on airway neurons and can mediate neurogenic inflammation, it was suggested that neuronal TRPA1 controls asthmatic phenotypes in the OVA model. Activation of airway neurons by allergen could be a critical requirement for contribution of neuronal channels in regulation of asthma phenotype. According to our observations, OVA cannot activate TRPA1 on airway neurons. Therefore, we hypothesize that neuronal TRPA1 does not participate in regulation of asthmatic phenotypes in the OVA model. Therefore the aim of this study is to evaluate whether neuronal TRPA1 regulates eosinophilia, T cell polarization and airway hyperreactivity (AHR) in the OVA model. METHODS: We used conditional knock-out approach to specifically ablate TRPA1 in airway neurons of mice. Global TRPA1 knockout mice served as positive control. In the OVA model, asthma phenotypes were evaluated by total and differential immune cell counts from BALF, measuring Th1 and Th2 specific cytokines in BALF and lung, examining lung pathology and function by Flexivent. Data were analyzed using oneor two-way ANOVA. RESULTS: We observed attenuation of eosinophilia, Th2 responses and AHR in the OVA model after global, but not airway neuron-specific ablation of TRPA1. CONCLUSIONS: Non-neuronal TRPA1 mediates allergic asthma phenotypes in the OVA model.

Research paper thumbnail of Anti-inflammatory effects of aerobic exercise in mice exposed to air pollution

Medicine and science in sports and exercise, 2012

Exposure to diesel exhaust particles (DEP) results in lung inflammation. Regular aerobic exercise... more Exposure to diesel exhaust particles (DEP) results in lung inflammation. Regular aerobic exercise improves the inflammatory status in different pulmonary diseases. However, the effects of long-term aerobic exercise on the pulmonary response to DEP have not been investigated. The present study evaluated the effect of aerobic conditioning on the pulmonary inflammatory and oxidative responses of mice exposed to DEP. BALB/c mice were subjected to aerobic exercise five times per week for 5 wk, concomitantly with exposure to DEP (3 mg·mL(-1); 10 μL per mouse). The levels of exhaled nitric oxide, reactive oxygen species, cellularity, interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were analyzed in bronchoalveolar lavage fluid, and the density of neutrophils and the volume proportion of collagen fibers were measured in the lung parenchyma. The cellular density of leukocytes expressing IL-1β, keratinocyte chemoattractant (KC), and TNF-α in lung parenchyma was evaluated with immunoh...

Research paper thumbnail of Cigarette smoke dissociates inflammation and lung remodeling in OVA-sensitized and challenged mice

Respiratory Physiology & Neurobiology, 2012

Research paper thumbnail of Role of nitric oxide in hyperpnea-induced bronchoconstriction and airway microvascular permeability in guinea pigs

Experimental Lung Research, 2010

Research paper thumbnail of Spinal Anesthesia Increases Pulmonary Responsiveness to Methacholine in Guinea Pigs

Anesthesia & Analgesia, 1998

It has been postulated that regional anesthesia, when feasible, is the best anesthetic approach i... more It has been postulated that regional anesthesia, when feasible, is the best anesthetic approach in asthmatic patients. However, there are reports of severe bronchospasm during regional anesthesia. In the present study, we developed an experimental model of spinal (subarachnoid) anesthesia in guinea pigs and studied respiratory system responsiveness to aerosolized methacholine. The animals received sodium pentobarbital (50 mg/kg intraperitoneally), a tracheotomy, and mechanical ventilation. Four groups of animals were studied: guinea pigs that received spinal anesthesia with lidocaine (500 PL of 2% solution) (n = 7); guinea pigs that received spinal administration of isotonic sodium chloride solution (500 pL) (n = 7); guinea pigs that received an intraperitoneal injection of lidocaine (500 PL of 2% solution) (I? = 6); and control guinea pigs (n = 7). The concentration of methacholine chloride that resulted in 50% of the maximal value of respiratory system elastance was lower in guinea pigs that received spinal anesthesia compared with the other three groups (P C= 0.005 for control group, P < 0.01 for spinal saline group, and P < 0.05 for intraperitoneal lidocaine group). Our results suggest that spinal anesthesia results in an increase in pulmonary responsiveness to bronchoconstrictive stimuli. Implications:

Research paper thumbnail of Creatine Supplementation Exacerbates Allergic Lung Inflammation and Airway Remodeling in Mice

American Journal of Respiratory Cell and Molecular Biology, 2007

Creatine supplement is the most popular nutritional supplement, and has various metabolic functio... more Creatine supplement is the most popular nutritional supplement, and has various metabolic functions and sports medicine applications. Creatine supplementation increases muscle mass and can decrease muscular inflammation. Some studies have also suggested a beneficial role of creatine supplementation on chronic pulmonary diseases such as chronic obstructive pulmonary disease and cystic fibrosis. Among athletes, the prevalence of asthma is high, and many of these individuals may be taking creatine. However, the effects of creatine supplementation on chronic pulmonary diseases of allergic origin have not been investigated. In the present study, we analyzed the effects of creatine supplementation on a model of chronic allergic lung inflammation. Thirty-one Balb/c mice were divided into four groups: control, creatine (Cr), ovalbumin (OVA), and OVA1Cr. OVA and OVA1Cr groups were sensitized with intraperitoneal injections of OVA on Days 0, 14, 28, and 42. OVA challenge (OVA 1%) and Cr treatment (0.5 g/kg/d) were initiated on Day 21 and lasted until Day 53. We determined the index of hyperresponsiveness, the serum levels of OVA-specific immunoglobulin (Ig)E and IgG 1 , and the total and differential cell counts in bronchoalveolar lavage fluid. We also quantified airway inflammation, and the airway density of IL-41, IL-51, IL-21, IFN-g1, and insulin-like growth factor (IGF)-11 cells, collagen and elastic fibers, and airway smooth muscle thickness. Our results showed that creatine in OVA-sensitized mice increased hyperresponsiveness; eosinophilic inflammation; airway density of IL-41, IL-51, and IGF-1 inflammatory cells; airway collagen and elastin content; and smooth muscle thickness. The results show that creatine supplementation exacerbates the lung allergic response to OVA through a T helper cell type 2 pathway and increased IGF-1 expression.

Research paper thumbnail of Capsaicin-induced release of VIP-like immunoreactivity: modulation by enzyme inhibitors

The American journal of physiology

... ADRIANA S. LEME, FERNANDA M. ARANTES, EDNA AL MALDONADO, MARIA DO PATROCXNIO TN WARTH, AND MI... more ... ADRIANA S. LEME, FERNANDA M. ARANTES, EDNA AL MALDONADO, MARIA DO PATROCXNIO TN WARTH, AND MILTON A. MARTINS Departments of Pathology and Medicine, Faculty of Medicine, University of StEo Paulo 01246-903, Brazil ...

Research paper thumbnail of Increased Airway Reactivity and Hyperinsulinemia in Obese Mice Are Linked by ERK Signaling in Brain Stem Cholinergic Neurons

Cell Reports, 2015

Obesity is a major risk factor for asthma, which is characterized by airway hyperreactivity (AHR)... more Obesity is a major risk factor for asthma, which is characterized by airway hyperreactivity (AHR). In obesity-associated asthma, AHR may be regulated by non-TH2 mechanisms. We hypothesized that airway reactivity is regulated by insulin in the CNS, and that the high levels of insulin associated with obesity contribute to AHR. We found that intracerebroventricular (ICV)-injected insulin increases airway reactivity in wild-type, but not in vesicle acetylcholine transporter knockdown (VAChT KD(HOM-/-)), mice. Either neutralization of central insulin or inhibition of extracellular signal-regulated kinases (ERK) normalized airway reactivity in hyperinsulinemic obese mice. These effects were mediated by insulin in cholinergic nerves located at the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (NA), which convey parasympathetic outflow to the lungs. We propose that increased insulin-induced activation of ERK in parasympathetic pre-ganglionic nerves contributes to AHR in obese mice, suggesting a drug-treatable link between obesity and asthma.

Research paper thumbnail of Airborne pollutant ROFA enhances the allergic airway inflammation through direct modulation of dendritic cells in an uptake-dependent mechanism

International Immunopharmacology, 2014

Studies suggest that airborne pollutants are important cofactors in the exacerbation of lung dise... more Studies suggest that airborne pollutants are important cofactors in the exacerbation of lung diseases. The role of DC on the exacerbation of lung inflammation induced by particulate matter pollutants is unclear. We evaluated the effects of residual oil fly ash (ROFA) on the phenotype and function of bone marrow-derived dendritic cells (BMDCs) in vitro and lung dendritic cells (DCs) in vivo, and the subsequent T-cell response. In a model of asthma, exposure to ROFA exacerbated pulmonary inflammation, which was attributed to the increase of eosinophils, IL-5- and IFN-γ-producing T cells, and goblet cells as well as decreased number of Treg and pDC. However, the ROFA showed no ability to modulate the production of anaphylactic IgE. In vitro studies showed that ROFA directly induced the maturation of DCs up-regulating the expression of co-stimulatory molecules and cytokines and MMP production in an uptake-dependent and oxidative stress-dependent manner. Furthermore, ROFA-pulsed BMDC transferred to allergic mice exacerbated eosinophilic inflammation as well as promoted increased epithelial and goblet cells changes. Thus, pollutants may constitute an important and risk factor in the exacerbation of asthma with inhibition of the negative regulatory signals in the lung, with enhanced mDC activation that sustains the recruitment of effector T lymphocytes and eosinophil.

Research paper thumbnail of Oral tolerance attenuates airway inflammation and remodeling in a model of chronic pulmonary allergic inflammation

Respiratory Physiology & Neurobiology, 2009

We investigated the effects of oral tolerance (OT) in controlling inflammatory response, hyperres... more We investigated the effects of oral tolerance (OT) in controlling inflammatory response, hyperresponsiveness and airway remodeling in guinea pigs (GP) with chronic allergic inflammation. Animals received seven inhalations of ovalbumin (1-5mg/mL-OVA group) or normal saline (NS group). OT was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st ovalbumin inhalation (OT1 group) or after the 4th (OT2 group). The induction of OT in sensitized animals decreased the elastance of respiratory system (Ers) response after both antigen and methacholine challenges, peribronchial edema formation, eosinophilic airway infiltration, eosinophilopoiesis, and airways collagen and elastic fiber content compared to OVA group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). The number of mononuclear cells and resistance of respiratory system (Rrs) responses after antigen and methacholine challenges were decreased only in OT2 group compared to OVA group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Concluding, our results show that inducing OT attenuates airway remodeling as well as eosinophilic inflammation and respiratory system mechanics.

Research paper thumbnail of Effects of Mannitol on the Acute Lung Injury Induced by Oleic Acid in Rats

Shock, 2001

Our purpose was to evaluate the pulmonary effects of mannitol infusion in a rat model of acute lu... more Our purpose was to evaluate the pulmonary effects of mannitol infusion in a rat model of acute lung injury induced by oleic acid (OA) to compare the effects of mannitol to those of another diuretic, furosemide (FUR), and to assess if mannitol effects remained after correction of the volume depletion induced by this agent. Acute lung injury was induced in Wistar rats by intravenous administration of 100 mg/kg of OA. Mannitol (1 mL of a 20% solution) was infused either 15 min before or 2 h after OA infusion. FUR was infused intravenously in a dose (1 mg/kg) that induced a similar amount of diuresis compared to mannitol. We also studied rats that received NaCl 0.9% infusion to correct for volume losses induced by mannitol. The severity of the acute lung injury was evaluated by morphometric studies of the lungs 4 h after OA infusion. The amount of intraalveolar fluid accumulation and the intensity of alveolar distention and collapse were evaluated. Mannitol infusion either 15 min before or 2 h after OA administration resulted in a significant decrease in the amount of intraalveolar edema and alveolar distention and collapse (P &lt; 0.001). FUR administration before OA infusion had an effect similar to mannitol. We did not observe any significant effect of mannitol when the rats received saline infusion to correct for diuresis induced by mannitol. We conclude that mannitol decreases the severity of pulmonary injury induced by OA in rats. This effect is mainly due to its diuretic properties.

Research paper thumbnail of A RAT MODEL OF ACUTE LUNG INJURY INDUCED BY CARDIOPULMONARY BYPASS

Shock, 2001

Impaired lung function is still a major complication after cardiac surgery with cardiopulmonary b... more Impaired lung function is still a major complication after cardiac surgery with cardiopulmonary bypass. The purpose of the present study was to develop an experimental model of acute pulmonary injury induced by cardiopulmonary bypass in Wistar rats. Cardiopulmonary bypass was performed for 60 min using a non-pulsatile roller pump and a membrane oxygenator (n = 8 for cardiopulmonary bypass group and n = 7 for control rats). We measured tracheal pressure, airflow, and lung volume changes and obtained pulmonary resistance and dynamic elastance. After the cardiopulmonary bypass, lungs were submitted to a quick-freezing protocol and morphometric analysis was performed. There was a time-dependent increase in dynamic elastance, but not pulmonary resistance, only in the rats submitted to cardiopulmonary bypass (P = 0.005). Lungs from animals submitted to cardiopulmonary bypass showed significantly more alveolar hemorrhage (P = 0.025) and edema (P = 0.021), as well as perivascular edema (P = 0.003) when compared to control rats. In our experimental model, rats submitted to cardiopulmonary bypass developed acute pulmonary changes similar to the early phase of acute pulmonary distress syndrome. Cardiopulmonary bypass resulted in an increase in pulmonary elastance without changes in resistance. This experimental model is suitable for studies concerning the mechanisms of acute lung injury induced by cardiopulmonary bypass.

Research paper thumbnail of Qualidade de vida do estudante de medicina

Revista de Medicina, 2019

Introdução: A qualidade de vida e a saúde mental dos estudantes de medicina podem afetar o seu de... more Introdução: A qualidade de vida e a saúde mental dos estudantes de medicina podem afetar o seu desempenho acadêmico, suas habilidades e atitudes com pacientes. Evidências recentes confirmam a importância do ambiente educacional como um dos determinantes da saúde mental e qualidade de vida. Este estudo teve o objetivo de avaliar diferentes aspectos da qualidade de vida dos estudantes de medicina brasileiros em todos os anos do curso. Casuística e Métodos: Estudo transversal de abrangência nacional, com a utilização de questionário validado de qualidade de vida específico para o estudante da área da saúde (Veras-q). Resultados: De uma amostra aleatória de 1.650 estudantes, em 22 escolas médicas de diferentes regiões do país, 1.350 (81,8%) participaram do estudo. Os coeficientes de alfa Cronbach dos domínios do Veras-q variaram entre 0,77 e 0,82. Estudantes do sexo feminino apresentaram menores escores de qualidade de vida nos domínios físico, psicológico e uso do tempo, quando compara...

Research paper thumbnail of The COVID-19 pandemic: time for medical teachers and students to overcome grief

Research paper thumbnail of Inhibition of Inflammation and Mucus Production By Bordetella Pertussis Whole-Cell Vaccine in a Murine Model of Allergic Rhinitis

Journal of Allergy and Clinical Immunology, 2016

Research paper thumbnail of Sensitization by subcutaneous route is superior to intraperitoneal route in induction of asthma by house dust mite in a murine mode

Einstein (São Paulo), 2015

To develop a new experimental model of chronic allergic pulmonary disease induced by house dust m... more To develop a new experimental model of chronic allergic pulmonary disease induced by house dust mite, with marked production of specific immunoglobulin E (IgE), eosinophilic inflammatory infiltrate in the airways and remodeling, comparing two different routes of sensitization. The protocol lasted 30 days. BALB/c mice were divided into six groups and were sensitized subcutaneously or intraperitoneally with saline (negative control), Dermatophagoides pteronyssinus (Der p) 50 or 500 mcg in three injections. Subsequently they underwent intranasal challenge with Der p or saline for 7 days and were sacrificed 24 hours after the last challenge. We evaluated the titration of specific IgE anti-Der p, eosinophilic density in peribronchovascular space and airway remodeling. Both animals sensitized intraperitoneally and subcutaneously produced specific IgE anti-Der p. Peribronchovascular eosinophilia increased only in mice receiving lower doses of Der p. However, only the group sensitized with Der p 50 mcg through subcutaneously route showed significant airway remodeling. In this murine model of asthma, both pathways of sensitization led to the production of specific IgE and eosinophilia in the airways. However, only the subcutaneously route was able to induce remodeling. Furthermore, lower doses of Der p used in sensitization were better than higher ones, suggesting immune tolerance. Further studies are required to evaluate the efficacy of this model in the development of bronchial hyperresponsiveness, but it can already be replicated in experiments to create new therapeutic drugs or immunotherapeutic strategies.

Research paper thumbnail of Effects of acute hypochlorite exposure in OVA-sensitized and challenged mice

European Respiratory Journal, 2015

Research paper thumbnail of BmTI-A, a serine protease inhibitor, reduces the chronic allergic lung inflammation in a mice model

European Respiratory Journal, 2015

Research paper thumbnail of Inflammatory and functional responses after (bio)diesel exhaust exposure in an asthmatic mice model – A comparison between diesel and biodiesel

European Respiratory Journal, 2015

Research paper thumbnail of Efeitos do resíduo da queima de óleo diesel (ROFA) e da inflamação pulmonar alérgica crônica em três linhagens de camundongos

Research paper thumbnail of Bordetella Pertussis Whole-Cell Vaccine Inhibits Specific IgE, Inflammation and Airway Remodeling in a Murine Model of Asthma

Journal of Allergy and Clinical Immunology, 2015

RATIONALE: Axon reflex theory was proposed to explain the involvement of afferent airway nerves i... more RATIONALE: Axon reflex theory was proposed to explain the involvement of afferent airway nerves in regulation allergic asthma phenotypes. Thus, afferent airway nerve ablation affects asthma phenotype in the ovalbumin (OVA) allergic asthma model. The regulation of asthma phenotypes by transient receptor potential A1 (TRPA1) in the OVA model has also been reported. Since TRPA1 is mainly expressed on airway neurons and can mediate neurogenic inflammation, it was suggested that neuronal TRPA1 controls asthmatic phenotypes in the OVA model. Activation of airway neurons by allergen could be a critical requirement for contribution of neuronal channels in regulation of asthma phenotype. According to our observations, OVA cannot activate TRPA1 on airway neurons. Therefore, we hypothesize that neuronal TRPA1 does not participate in regulation of asthmatic phenotypes in the OVA model. Therefore the aim of this study is to evaluate whether neuronal TRPA1 regulates eosinophilia, T cell polarization and airway hyperreactivity (AHR) in the OVA model. METHODS: We used conditional knock-out approach to specifically ablate TRPA1 in airway neurons of mice. Global TRPA1 knockout mice served as positive control. In the OVA model, asthma phenotypes were evaluated by total and differential immune cell counts from BALF, measuring Th1 and Th2 specific cytokines in BALF and lung, examining lung pathology and function by Flexivent. Data were analyzed using oneor two-way ANOVA. RESULTS: We observed attenuation of eosinophilia, Th2 responses and AHR in the OVA model after global, but not airway neuron-specific ablation of TRPA1. CONCLUSIONS: Non-neuronal TRPA1 mediates allergic asthma phenotypes in the OVA model.

Research paper thumbnail of Anti-inflammatory effects of aerobic exercise in mice exposed to air pollution

Medicine and science in sports and exercise, 2012

Exposure to diesel exhaust particles (DEP) results in lung inflammation. Regular aerobic exercise... more Exposure to diesel exhaust particles (DEP) results in lung inflammation. Regular aerobic exercise improves the inflammatory status in different pulmonary diseases. However, the effects of long-term aerobic exercise on the pulmonary response to DEP have not been investigated. The present study evaluated the effect of aerobic conditioning on the pulmonary inflammatory and oxidative responses of mice exposed to DEP. BALB/c mice were subjected to aerobic exercise five times per week for 5 wk, concomitantly with exposure to DEP (3 mg·mL(-1); 10 μL per mouse). The levels of exhaled nitric oxide, reactive oxygen species, cellularity, interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were analyzed in bronchoalveolar lavage fluid, and the density of neutrophils and the volume proportion of collagen fibers were measured in the lung parenchyma. The cellular density of leukocytes expressing IL-1β, keratinocyte chemoattractant (KC), and TNF-α in lung parenchyma was evaluated with immunoh...

Research paper thumbnail of Cigarette smoke dissociates inflammation and lung remodeling in OVA-sensitized and challenged mice

Respiratory Physiology & Neurobiology, 2012

Research paper thumbnail of Role of nitric oxide in hyperpnea-induced bronchoconstriction and airway microvascular permeability in guinea pigs

Experimental Lung Research, 2010

Research paper thumbnail of Spinal Anesthesia Increases Pulmonary Responsiveness to Methacholine in Guinea Pigs

Anesthesia & Analgesia, 1998

It has been postulated that regional anesthesia, when feasible, is the best anesthetic approach i... more It has been postulated that regional anesthesia, when feasible, is the best anesthetic approach in asthmatic patients. However, there are reports of severe bronchospasm during regional anesthesia. In the present study, we developed an experimental model of spinal (subarachnoid) anesthesia in guinea pigs and studied respiratory system responsiveness to aerosolized methacholine. The animals received sodium pentobarbital (50 mg/kg intraperitoneally), a tracheotomy, and mechanical ventilation. Four groups of animals were studied: guinea pigs that received spinal anesthesia with lidocaine (500 PL of 2% solution) (n = 7); guinea pigs that received spinal administration of isotonic sodium chloride solution (500 pL) (n = 7); guinea pigs that received an intraperitoneal injection of lidocaine (500 PL of 2% solution) (I? = 6); and control guinea pigs (n = 7). The concentration of methacholine chloride that resulted in 50% of the maximal value of respiratory system elastance was lower in guinea pigs that received spinal anesthesia compared with the other three groups (P C= 0.005 for control group, P < 0.01 for spinal saline group, and P < 0.05 for intraperitoneal lidocaine group). Our results suggest that spinal anesthesia results in an increase in pulmonary responsiveness to bronchoconstrictive stimuli. Implications:

Research paper thumbnail of Creatine Supplementation Exacerbates Allergic Lung Inflammation and Airway Remodeling in Mice

American Journal of Respiratory Cell and Molecular Biology, 2007

Creatine supplement is the most popular nutritional supplement, and has various metabolic functio... more Creatine supplement is the most popular nutritional supplement, and has various metabolic functions and sports medicine applications. Creatine supplementation increases muscle mass and can decrease muscular inflammation. Some studies have also suggested a beneficial role of creatine supplementation on chronic pulmonary diseases such as chronic obstructive pulmonary disease and cystic fibrosis. Among athletes, the prevalence of asthma is high, and many of these individuals may be taking creatine. However, the effects of creatine supplementation on chronic pulmonary diseases of allergic origin have not been investigated. In the present study, we analyzed the effects of creatine supplementation on a model of chronic allergic lung inflammation. Thirty-one Balb/c mice were divided into four groups: control, creatine (Cr), ovalbumin (OVA), and OVA1Cr. OVA and OVA1Cr groups were sensitized with intraperitoneal injections of OVA on Days 0, 14, 28, and 42. OVA challenge (OVA 1%) and Cr treatment (0.5 g/kg/d) were initiated on Day 21 and lasted until Day 53. We determined the index of hyperresponsiveness, the serum levels of OVA-specific immunoglobulin (Ig)E and IgG 1 , and the total and differential cell counts in bronchoalveolar lavage fluid. We also quantified airway inflammation, and the airway density of IL-41, IL-51, IL-21, IFN-g1, and insulin-like growth factor (IGF)-11 cells, collagen and elastic fibers, and airway smooth muscle thickness. Our results showed that creatine in OVA-sensitized mice increased hyperresponsiveness; eosinophilic inflammation; airway density of IL-41, IL-51, and IGF-1 inflammatory cells; airway collagen and elastin content; and smooth muscle thickness. The results show that creatine supplementation exacerbates the lung allergic response to OVA through a T helper cell type 2 pathway and increased IGF-1 expression.

Research paper thumbnail of Capsaicin-induced release of VIP-like immunoreactivity: modulation by enzyme inhibitors

The American journal of physiology

... ADRIANA S. LEME, FERNANDA M. ARANTES, EDNA AL MALDONADO, MARIA DO PATROCXNIO TN WARTH, AND MI... more ... ADRIANA S. LEME, FERNANDA M. ARANTES, EDNA AL MALDONADO, MARIA DO PATROCXNIO TN WARTH, AND MILTON A. MARTINS Departments of Pathology and Medicine, Faculty of Medicine, University of StEo Paulo 01246-903, Brazil ...

Research paper thumbnail of Increased Airway Reactivity and Hyperinsulinemia in Obese Mice Are Linked by ERK Signaling in Brain Stem Cholinergic Neurons

Cell Reports, 2015

Obesity is a major risk factor for asthma, which is characterized by airway hyperreactivity (AHR)... more Obesity is a major risk factor for asthma, which is characterized by airway hyperreactivity (AHR). In obesity-associated asthma, AHR may be regulated by non-TH2 mechanisms. We hypothesized that airway reactivity is regulated by insulin in the CNS, and that the high levels of insulin associated with obesity contribute to AHR. We found that intracerebroventricular (ICV)-injected insulin increases airway reactivity in wild-type, but not in vesicle acetylcholine transporter knockdown (VAChT KD(HOM-/-)), mice. Either neutralization of central insulin or inhibition of extracellular signal-regulated kinases (ERK) normalized airway reactivity in hyperinsulinemic obese mice. These effects were mediated by insulin in cholinergic nerves located at the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (NA), which convey parasympathetic outflow to the lungs. We propose that increased insulin-induced activation of ERK in parasympathetic pre-ganglionic nerves contributes to AHR in obese mice, suggesting a drug-treatable link between obesity and asthma.

Research paper thumbnail of Airborne pollutant ROFA enhances the allergic airway inflammation through direct modulation of dendritic cells in an uptake-dependent mechanism

International Immunopharmacology, 2014

Studies suggest that airborne pollutants are important cofactors in the exacerbation of lung dise... more Studies suggest that airborne pollutants are important cofactors in the exacerbation of lung diseases. The role of DC on the exacerbation of lung inflammation induced by particulate matter pollutants is unclear. We evaluated the effects of residual oil fly ash (ROFA) on the phenotype and function of bone marrow-derived dendritic cells (BMDCs) in vitro and lung dendritic cells (DCs) in vivo, and the subsequent T-cell response. In a model of asthma, exposure to ROFA exacerbated pulmonary inflammation, which was attributed to the increase of eosinophils, IL-5- and IFN-γ-producing T cells, and goblet cells as well as decreased number of Treg and pDC. However, the ROFA showed no ability to modulate the production of anaphylactic IgE. In vitro studies showed that ROFA directly induced the maturation of DCs up-regulating the expression of co-stimulatory molecules and cytokines and MMP production in an uptake-dependent and oxidative stress-dependent manner. Furthermore, ROFA-pulsed BMDC transferred to allergic mice exacerbated eosinophilic inflammation as well as promoted increased epithelial and goblet cells changes. Thus, pollutants may constitute an important and risk factor in the exacerbation of asthma with inhibition of the negative regulatory signals in the lung, with enhanced mDC activation that sustains the recruitment of effector T lymphocytes and eosinophil.

Research paper thumbnail of Oral tolerance attenuates airway inflammation and remodeling in a model of chronic pulmonary allergic inflammation

Respiratory Physiology & Neurobiology, 2009

We investigated the effects of oral tolerance (OT) in controlling inflammatory response, hyperres... more We investigated the effects of oral tolerance (OT) in controlling inflammatory response, hyperresponsiveness and airway remodeling in guinea pigs (GP) with chronic allergic inflammation. Animals received seven inhalations of ovalbumin (1-5mg/mL-OVA group) or normal saline (NS group). OT was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st ovalbumin inhalation (OT1 group) or after the 4th (OT2 group). The induction of OT in sensitized animals decreased the elastance of respiratory system (Ers) response after both antigen and methacholine challenges, peribronchial edema formation, eosinophilic airway infiltration, eosinophilopoiesis, and airways collagen and elastic fiber content compared to OVA group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). The number of mononuclear cells and resistance of respiratory system (Rrs) responses after antigen and methacholine challenges were decreased only in OT2 group compared to OVA group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Concluding, our results show that inducing OT attenuates airway remodeling as well as eosinophilic inflammation and respiratory system mechanics.

Research paper thumbnail of Effects of Mannitol on the Acute Lung Injury Induced by Oleic Acid in Rats

Shock, 2001

Our purpose was to evaluate the pulmonary effects of mannitol infusion in a rat model of acute lu... more Our purpose was to evaluate the pulmonary effects of mannitol infusion in a rat model of acute lung injury induced by oleic acid (OA) to compare the effects of mannitol to those of another diuretic, furosemide (FUR), and to assess if mannitol effects remained after correction of the volume depletion induced by this agent. Acute lung injury was induced in Wistar rats by intravenous administration of 100 mg/kg of OA. Mannitol (1 mL of a 20% solution) was infused either 15 min before or 2 h after OA infusion. FUR was infused intravenously in a dose (1 mg/kg) that induced a similar amount of diuresis compared to mannitol. We also studied rats that received NaCl 0.9% infusion to correct for volume losses induced by mannitol. The severity of the acute lung injury was evaluated by morphometric studies of the lungs 4 h after OA infusion. The amount of intraalveolar fluid accumulation and the intensity of alveolar distention and collapse were evaluated. Mannitol infusion either 15 min before or 2 h after OA administration resulted in a significant decrease in the amount of intraalveolar edema and alveolar distention and collapse (P &lt; 0.001). FUR administration before OA infusion had an effect similar to mannitol. We did not observe any significant effect of mannitol when the rats received saline infusion to correct for diuresis induced by mannitol. We conclude that mannitol decreases the severity of pulmonary injury induced by OA in rats. This effect is mainly due to its diuretic properties.

Research paper thumbnail of A RAT MODEL OF ACUTE LUNG INJURY INDUCED BY CARDIOPULMONARY BYPASS

Shock, 2001

Impaired lung function is still a major complication after cardiac surgery with cardiopulmonary b... more Impaired lung function is still a major complication after cardiac surgery with cardiopulmonary bypass. The purpose of the present study was to develop an experimental model of acute pulmonary injury induced by cardiopulmonary bypass in Wistar rats. Cardiopulmonary bypass was performed for 60 min using a non-pulsatile roller pump and a membrane oxygenator (n = 8 for cardiopulmonary bypass group and n = 7 for control rats). We measured tracheal pressure, airflow, and lung volume changes and obtained pulmonary resistance and dynamic elastance. After the cardiopulmonary bypass, lungs were submitted to a quick-freezing protocol and morphometric analysis was performed. There was a time-dependent increase in dynamic elastance, but not pulmonary resistance, only in the rats submitted to cardiopulmonary bypass (P = 0.005). Lungs from animals submitted to cardiopulmonary bypass showed significantly more alveolar hemorrhage (P = 0.025) and edema (P = 0.021), as well as perivascular edema (P = 0.003) when compared to control rats. In our experimental model, rats submitted to cardiopulmonary bypass developed acute pulmonary changes similar to the early phase of acute pulmonary distress syndrome. Cardiopulmonary bypass resulted in an increase in pulmonary elastance without changes in resistance. This experimental model is suitable for studies concerning the mechanisms of acute lung injury induced by cardiopulmonary bypass.